Doctors, researchers and patient groups will be encouraged to suggest alternative therapeutic uses for existing medicines under a new initiative from the TGA.

Known as the Medicines Repurposing Program, the scheme aims to enable new clinical uses of existing medicines with a streamlined pathway for new registered indications for medicines approved in Australia, many of which will have been used ‘off-label’ for years.

Whilst this may be accepted clinical practice, obtaining formal regulatory approval for the repurposed indication can lead to wider and safer use, according to the government.

Repurposing would require the evidence base for such clinical use to be independently reviewed and found sufficient, and that the benefits of such use shown to outweigh the risks, the TGA said in a consultation paper last year (link here).

“Regulatory approval of the indication would also address the medico-legal concerns that can arise from off label use, increase patient and healthcare practitioner confidence and enable the possibility of reimbursement for the indication through listing on the PBS,” the paper said.

It notes that, recently, repurposing older medicines has been a prominent area of research for potential COVID-19 treatments, but pathways remain slow moving and cumbersome.

Beyond that, the TGA, often in cooperation with the relevant specialist medical college, has promoted repurposing directly with sponsors, but with only “mixed success”, according to the agency (see examples below).

Developed as part of the National Strategic Action Plan for Rare Diseases, the program will accept nominations from any organisation or individual, but will target medicines for which a significant public health benefit has been identified but with little or no commercial incentive for a sponsor to pursue regulatory approval and PBS listing.

Nominations will be assessed by a dedicated program team before being put forward to the TGA and Pharmaceutical Benefits Advisory Committee for approval.

The first batch of nominations will be accepted until 17 April, via a form on the TGA website (link here).

A repurposing scheme was a key recommendation of a 2021 parliamentary inquiry into approval processes for new drugs and technologies.

In November 2023 the government agreed with the inquiry report’s recommendation to establish a repurposing program “to target medicines for which a significant public health benefit has been identified but there is little or no commercial incentive for a sponsor to pursue regulatory approval and PBS listing to make this use more accessible.”

Repurposing in Australia: recent successes and failures

Tamoxifen

Tamoxifen has been in clinical use for the treatment of breast cancer since the 1970s and is registered and reimbursed for this indication in Australia. Tamoxifen was also approved by the United States Food and Drug Administration (US FDA) in 1998 for the reduction in breast cancer incidence in high risk women, but was not approved in Australia or reimbursed for this indication despite wide ‘off-label’ use for this purpose supported by recommendations in Australian and international guidelines.

To facilitate registration of the ‘off-label’ indication, the TGA worked with the innovator sponsor of tamoxifen to develop a literature based submission. This approach streamlined the application process with a focus on safety and efficacy without the requirement for quality or nonclinical information (as this was already established). Despite tamoxifen being off-patent at the time, none of the generic manufacturers took an interest in applying to extend indications because, as stated at the time, this was not part of their usual business model.

Rifampicin

Rifampicin was as an important ‘off-label’ treatment option for Buruli ulcer, a skin/soft tissue infection due to a mycobacterium, of growing concern in coastal parts of Victoria.

Although the market for this indication is quite small, a regulatory application was received and was approved by the TGA in October 2020 (in combination with another antibiotic). Rifampicin was subsequently listed on the PBS.

Dacarbazine

At the request of clinical groups, the TGA investigated the potential for repurposing dacarbazine for early stage Hodgkin’s Lymphoma. Despite repeated approaches to sponsors, no submissions were received. The TGA cannot compel a sponsor to make a submission.

These examples demonstrate that while some successes have been had, barriers remain to the repurposing of medicines.